Genetic analysis of a case of mosaic trisomy 21 associated with autism spectrum disorder

Objective: To explore the genetic basis for a child with autism spectrum disorder (ASD) and congenital heart disease.

Methods: G-banded chromosomal karyotyping was carried out for the patient and his parents. The child was also subjected to whole exome sequencing (WES) and low-coverage massively parallel copy number variation sequencing (CNV-seq). The result was validated by chromosomal microarray analysis (CMA).

Results: The karyotype of the patient and his parents were normal. No significant genetic variation was found by WES. However, CNV-seq has discovered a 47, XY, +21 [10%]/46,XY [90%] mosaicism in the patient. The result was confirmed by CMA.

Conclusions: In addition to Down syndrome, low proportion mosaic trisomy 21 is also associated with ASD. WES and CNV-seq can enable accurate diagnosis for patient with unexplained ASD.